PLCD4_MACFA
ID PLCD4_MACFA Reviewed; 799 AA.
AC Q4R6L3;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4;
DE EC=3.1.4.11 {ECO:0000250|UniProtKB:Q9BRC7};
DE AltName: Full=Phosphoinositide phospholipase C-delta-4;
DE AltName: Full=Phospholipase C-delta-4;
DE Short=PLC-delta-4;
GN Name=PLCD4; ORFNames=QtsA-17742;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2)
CC to generate 2 second messenger molecules diacylglycerol (DAG) and
CC inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of
CC protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular
CC stores. Required for acrosome reaction in sperm during fertilization,
CC probably by acting as an important enzyme for intracellular Ca(2+)
CC mobilization in the zona pellucida-induced acrosome reaction. May play
CC a role in cell growth. Modulates the liver regeneration in cooperation
CC with nuclear PKC. Overexpression up-regulates the Erk signaling pathway
CC and proliferation (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-
CC diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456,
CC ChEBI:CHEBI:203600; EC=3.1.4.11;
CC Evidence={ECO:0000250|UniProtKB:Q9BRC7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180;
CC Evidence={ECO:0000250|UniProtKB:Q9BRC7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O =
CC 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H(+);
CC Xref=Rhea:RHEA:43484, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:57880, ChEBI:CHEBI:58433;
CC Evidence={ECO:0000250|UniProtKB:Q9BRC7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43485;
CC Evidence={ECO:0000250|UniProtKB:Q9BRC7};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 5 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound
CC to the C2 domain. {ECO:0000250};
CC -!- SUBUNIT: Interacts with GRIP1 (By similarity). Interacts (via GBA
CC motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3
CC (inactive GDP-bound form); low-affinity interaction (By similarity).
CC {ECO:0000250|UniProtKB:Q8K3R3, ECO:0000250|UniProtKB:Q9BRC7}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Endoplasmic reticulum {ECO:0000250}. Note=Localizes primarily to
CC intracellular membranes mostly to the endoplasmic reticulum.
CC {ECO:0000250}.
CC -!- DOMAIN: The PDZ-binding motif mediates the interaction with GRIP1.
CC {ECO:0000250}.
CC -!- DOMAIN: The C2 domain mediates pre-localization to the membrane prior
CC to Ca(2+) import and non-selective Ca(2+)-mediated targeting to various
CC cellular membranes. {ECO:0000250}.
CC -!- DOMAIN: The PH domain is not a critical determinant of the membrane
CC localization. {ECO:0000250}.
CC -!- DOMAIN: The GBA (G-alpha binding and activating) motif mediates binding
CC to the alpha subunits of guanine nucleotide-binding proteins (G
CC proteins). {ECO:0000250|UniProtKB:Q9BRC7}.
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DR EMBL; AB169170; BAE01262.1; -; mRNA.
DR RefSeq; NP_001306482.1; NM_001319553.1.
DR AlphaFoldDB; Q4R6L3; -.
DR SMR; Q4R6L3; -.
DR STRING; 9541.XP_005574345.1; -.
DR PRIDE; Q4R6L3; -.
DR GeneID; 102122144; -.
DR CTD; 84812; -.
DR eggNOG; KOG0169; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IEA:UniProtKB-EC.
DR GO; GO:0007340; P:acrosome reaction; IEA:InterPro.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IEA:InterPro.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR Gene3D; 3.20.20.190; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR001192; PI-PLC_fam.
DR InterPro; IPR028387; PLC-delta4.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR InterPro; IPR015359; PLC_EF-hand-like.
DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom.
DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y.
DR PANTHER; PTHR10336; PTHR10336; 1.
DR PANTHER; PTHR10336:SF31; PTHR10336:SF31; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF09279; EF-hand_like; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00388; PI-PLC-X; 1.
DR Pfam; PF00387; PI-PLC-Y; 1.
DR PRINTS; PR00390; PHPHLIPASEC.
DR SMART; SM00239; C2; 1.
DR SMART; SM00054; EFh; 3.
DR SMART; SM00233; PH; 1.
DR SMART; SM00148; PLCXc; 1.
DR SMART; SM00149; PLCYc; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51695; SSF51695; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1.
DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1.
PE 2: Evidence at transcript level;
KW Calcium; Cytoplasm; Endoplasmic reticulum; Hydrolase; Lipid degradation;
KW Lipid metabolism; Membrane; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transducer.
FT CHAIN 1..799
FT /note="1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase delta-4"
FT /id="PRO_0000306825"
FT DOMAIN 16..124
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 134..169
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 170..205
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 206..237
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 290..435
FT /note="PI-PLC X-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT DOMAIN 530..646
FT /note="PI-PLC Y-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271"
FT DOMAIN 646..773
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 26..53
FT /note="Substrate binding"
FT /evidence="ECO:0000250"
FT MOTIF 213..243
FT /note="GBA"
FT /evidence="ECO:0000250|UniProtKB:Q9BRC7"
FT MOTIF 768..771
FT /note="PDZ-binding"
FT ACT_SITE 305
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT ACT_SITE 350
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT BINDING 147
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 149
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 151
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 153
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 158
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 185
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 194
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 306
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 335
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 337
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 384
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 433
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 435
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 559
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 586
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 687
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 689
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 713
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 742
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 743
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT BINDING 744
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000250"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62711"
SQ SEQUENCE 799 AA; 91437 MW; FE30A582F5FB7FAF CRC64;
MASLLQDRLT TDQDLLLMQE GMPMRKVRSK SWKKLRYFRL QNDGMTVWHA RQARGSAKPS
FSISDVETIR NGHDSELLRS LTEELPLEQG FTVVFHGRRS NLDLVANSVE EAQIWMRGLH
LLVDLVTSMD HQERLDQWLS DWFQRGDKNQ DGKMSFQEVQ RLLHLMNVEM DQEYAFSLFQ
AADTSQSGTL EGEEFVEFYK ALTKRAEVQE LFESFSADGQ KLTLLEFSDF LREEQKERDC
TSELALELID RYEPSDSGKL RHVLSMDGFL SYLCSKDGDI FNPACLPIYQ DMTQPLNHYF
ICSSHNTYLV GDQLCGQSSV EGYIRALKRG CRCVEVDVWD GPSGEPVVYH GHTLTSRILF
KDVVATVAQY AFQTSDYPVI LSLETHCSWE QQQTMARHLT EILGEQLLST TLDGVLPTQL
PSPEELRRKI LVKGKKLTLE EDLEYEEEEV EPGLEGEHES ELALESQFET ESEPEPQEQN
LQIKDKKKVV TCPLFCPSIC CQIVAQAPIS KPGSLLLSQQ KSKTILCPAL SSLVIYLKSV
SFRSFTHSKK HYHFYEISSF SETKAKRLIK EAGNEFVQHN TWQLSRVYPS GLRTDSSNYN
PQELWNAGCQ MVAMNMQTAG LEMDICDGHF RQNGGCGYVL KPDFLRDNQS SFHPERPISP
FKAQTLLIQV ISGQQLPKLN KTKEGSIVDP LVKVQIFGVR LDTARQETNY VENNGFNPYW
GQTLCFRVLV PELAMLRFVV MDYDWKSRND FIGQYTLPWS CMQQGYRHIH LLSKDGISLC
PASIFVYICI REGLEGDES
